PROJECT ABSTRACT Over half of the 6 million persons with opioid use disorder (OUD) in the United States also suffer from chronic pain, which reinforces a negative cycle of negative cycle of poor health outcomes and increased risk of illicit opioid use. There is a desperate, pressing need for innovative and equitable therapies to relieve suffering of patients with comorbid chronic pain and OUD. Mindfulness interventions are thought to affect pain and opioid use through directly increasing dispositional mindfulness and by indirectly decreasing stress response, improving cognitive processing of pain (e.g., pain acceptance), increasing positive affect, and by reducing opioid craving. Based on our group’s compelling pilot data, we will test the hypothesis that an immersive mindfulness VR intervention will improve pain and illicit opioid use among people with chronic pain and OUD. To do so, we will conduct a randomized controlled trial to test the efficacy of an on-site evidence-based immersive mindfulness VR treatment (RelieVRx) vs non- immersive VR (sham VR). We will enroll and randomize 185 participants with chronic pain and OUD to either twice-weekly RelieVRx or twice-weekly Sham VR over 8 weeks at OTPs in the Bronx, NY, the poorest borough in New York and a consistent epicenter for the opioid epidemic. Our co-primary outcomes are pain intensity and illicit opioid use at 12 weeks. We will test the effectiveness of immersive mindfulness VR on pain and illicit opioid use in patients with chronic pain and opioid use disorder enrolled at opioid treatment programs (Aim 1). We will examine daily effects of the intervention on mindfulness, stress, pain, opioid craving, and physiologic stress responses (Aim 2). Lastly, we will explore mechanisms underlying intervention effects (Aim 3). This highly innovative project utilizes novel and emerging technology to address critical gaps in care in vulnerable populations with comorbid chronic pain and OUD. Given our experience and expertise, our multi- disciplinary team is well positioned to test an immersive mindfulness VR intervention in an opioid treatment program.

PROJECT NARRATIVE Over half of the 6 million persons with opioid use disorder (OUD) in the United States also suffer from chronic pain, which reinforces a negative cycle of poor health outcomes and increased risk of illicit opioid use. We will test an evidence-based immersive mindfulness virtual reality intervention that has shown benefit in reducing pain and shows promise to reduce illicit opioid use within opioid treatment programs over 8 weeks. By testing the efficacy of the intervention within opioid treatment programs, this innovative study has the potential to change how opioid treatment programs deliver care to patients with chronic pain and OUD.